AGENDA 

FIFRA SCIENTIFIC ADVISORY PANEL (SAP) 

 OPEN MEETING 

 

February 2 – 5, 2010 

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805 

Docket Number: EPA-HQ-OPP- 2009-0851 

U.S. Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.) 

2777 S. Crystal Drive, Arlington, VA 22202 

Draft Framework and Case Studies on Atrazine, Human Incidents, and the 

Agricultural Health Study: Incorporation of Epidemiology and Human Incident 

Data into Human Health Risk Assessment 

Please note that all times are approximate (see note at end of Agenda). 

Tuesday, February 2, 2010 

8:30 A.M. Opening of Meeting and Administrative Procedures – Myrta R. 

Christian, M.S., Designated Federal Official, Office of Science 

Coordination and Policy, EPA 

8:35 A.M. Introduction and Identification of Panel Members – Steven G. 

Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair 

8:50 A.M. Welcome and Opening Remarks – Steven Bradbury, Ph.D., Acting 

Director, Office of Pesticide Programs, EPA 

9:00 A.M. Welcome and Opening Remarks – Tina E. Levine, Ph.D., Director, 

Health Effects Division, Office of Pesticide Programs, EPA 

9:15 A.M. Overview and Draft Framework for Incorporation of Epidemiology 

and Human Incident Data into Human Health Risk Assessment– Anna 

Lowit, Ph.D., Health Effects Division, Office of Pesticide Programs, EPA 

9:35 A.M Retrospective and Ecologic Non-Cancer Epidemiology Studies: 

Atrazine Studies – Aaron Niman, Health Effects Division, Office of 

Pesticide Programs, EPA

10:15 A.M. Break 

10:30 A.M. Overview of the Agricultural Health Study – Michael C.R. Alavanja, 

Dr.P.H. , Senior Investigator, Division of Cancer Epidemiology and 

Genetics, National Cancer Institute

11:10 A.M. The Agricultural Health Study & Office of Pesticide Programs: 

Comparison of Exposure Assessment Approaches: Shalu Shelat, 

Industrial Hygienist, Health Effects Division 

12:00 P.M. Lunch
1:40 P.M. Summary-- Anna Lowit, Ph.D., Health Effects Division, Office of Pesticide 

Programs, EPA 

2

1:00 P.M. Human Incident Data-- Retrospective Case Study Using Diazinon: 

Sarah Winfield, Biologist, Health Effects Division 

2:00 P.M. Public Comments 

3:00 P.M. Break 

3:15 P.M. Public Comments (continued) 

5:00 P.M. Adjourn

NOTE: Please be advised that agenda times are approximate; when the discussion for 

one topic is completed, discussions for the next topic will begin. For further information, 

please contact the Designated Federal Official for this meeting, Myrta R. Christian, via 

telephone: (202) 564-8498; fax: (202) 564-8382; or email: christian.myrta@epa.gov
 OPEN MEETING 

3

AGENDA 

FIFRA SCIENTIFIC ADVISORY PANEL (SAP) 

 

February 2 – 5, 2010 

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805 

Docket Number: EPA-HQ-OPP- 2009-0851 

U.S. Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.) 

2777 S. Crystal Drive, Arlington, VA 22202 

Draft Framework and Case Studies on Atrazine, Human Incidents, and the 

Agricultural Health Study: Incorporation of Epidemiology and Human Incident 

Data into Human Health Risk Assessment 

Please note that all times are approximate (see note at end of Agenda). 

Wednesday, February 3, 2010 

8:30 A.M. Opening of Meeting and Administrative Procedures – Myrta R. 

Christian, M.S, Designated Federal Official, Office of Science Coordination 

and Policy, EPA 

8:35 A.M. Introduction and Identification of Panel Members – Steven G. 

Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair 

8:50 A.M. Follow-up from Previous Day’s Discussion – TBD, Health Effects 

Division, Office of Pesticide Programs, EPA 

9:15 A.M. Charge to Panel – Question 1 

Draft Framework for Incorporating Human Epidemiologic & Incident Data in Risk 

Assessment

OPP’s draft framework describes a proposed weight of the evidence (WOE) evaluation that 

integrates science on exposure, pharmacokinetics, and mode of action derived from experimental 

animal and human in vivo and in vitro studies. This proposed WOE uses the “source-to-adverse 

outcome pathway” and the modified Bradford Hill criteria like that in the Mode of Action 

(MOA) Framework (Section IV of Draft Framework) as tools for organizing and evaluating 

these diverse types of data to determine the evidence available on the potential human health 

consequences of pesticide exposures. 

Question 1.1 Section II of the draft framework describes the major types of epidemiology studies

along with their strengths and limitations, factors to consider when reviewing epidemiology 
studies, and ways to use epidemiology data in risk assessment. Please comment on the 

soundness and completeness of these discussions. If appropriate, please include comments on 

additional factors for OPP to consider when evaluating the quality and weighing the utility of 

epidemiology studies in risk assessment/characterization. 

Question 1.2 Section III of the draft framework describes the major sources of human incident 

data along with their strengths and limitations. Section III also describes ways to use human 

incident data in risk assessment. Please comment on the soundness and completeness of these 

discussions. Please include comments on additional factors to consider when evaluating the 

quality and weighing the utility of human incident data in risk assessment/characterization. 

Question 1.3 Section IV of the draft framework describes a proposed WOE approach for 

evaluating human and experimental animal data from in vitro and in vivo studies. This proposed 

approach makes use of the “source to adverse outcome pathway” and the modified Bradford Hill 

criteria (like that in the MOA Framework) as tools for organizing, evaluating, and describing the 

human health consequence of a particular chemical based on the available data. Please comment 

on the proposed use of modified Bradford Hill criteria in the context of the source to adverse 

outcome pathway for integrating a variety of types of data at different levels of biological 

organization including human incident and epidemiologic data in risk assessment. 

4

10:15 A.M. Break

10:30 A.M. Charge to Panel – Question 1 (continued)

Question 1.4 OPP has extensive experience applying the MOA Framework to experimental 

animal data. However, OPP has not yet completed a WOE approach that also includes 

epidemiology or human incident data like that proposed in Section IV of the draft framework. 

Please include in your comments what, if any, additional scientific considerations not discussed 

in the draft framework OPP should take into account when conducting such WOE analyses.

11:30 A.M. Lunch 

12:45 P.M. Charge to Panel – Question 2 

Case Study A: Retrospective and Ecologic Non-Cancer Epidemiology Studies

OPP has a dual purpose for developing the Case study A on recent ecologic and retrospective 

epidemiology studies reporting adverse birth outcomes associated with atrazine exposure. First, 

the case study illustrates key methodological issues that OPP must consider when integrating 

ecologic and retrospective epidemiology studies in risk assessment/characterization. Second, 

this case study reviews several recent studies that will be considered in the re-evaluation of 

atrazine. Building on the feedback from the SAP at the February, 2010 meeting, these studies 

will be incorporated in the overall WOE analysis and risk characterization for atrazine. The 

atrazine WOE is scheduled for review by the FIFRA SAP in September, 2010. 

Question 2.1 As discussed in Question 1.1, the draft framework provides general descriptions of 

the strengths and limitations of ecologic and retrospective epidemiology studies with respect to 

human health risk assessment. Please describe what you consider to be characteristics of robust, 
Question 2.2 Ecologic and retrospective epidemiology studies are particularly useful in 

identifying new hypotheses about the human health effects of pesticide exposure and may 

confirm the human relevance of findings from experimental animal studies. However, these 

types of studies do not typically include robust characterization of exposure and they do not 

address confounding factors as well as prospective studies. Although there may be exceptions, 

generally, ecologic and retrospective epidemiology studies are not sufficiently robust for use in 

quantitative risk assessment (i.e., for use in deriving a point of departure or in quantitatively 

informing extrapolation factors, etc). In light of the strengths and limitations of ecologic and 

retrospective studies, please comment on appropriate ways to use of these types of epidemiology 

studies in risk assessment/characterization or their utility in problem formulation (e.g. defining 

additional analyses or research/testing). 

Question 2.3 The atrazine case study (Case study A) provides specific examples of ecologic and 

retrospective epidemiology studies. Please comment on OPP’s reviews of the studies discussed 

in Case study A. In your comments, please provide specific feedback on the OPP’s descriptions 

of each study design, exposure assessment, use of appropriate statistical methods, and ability to 

address bias and confounding in addition to other factors that may be important in the 

interpretation of these studies. 

5

well-designed ecologic and retrospective epidemiology studies. 

2:15 P.M. Break 

2:30 P.M. Charge to Panel – Question 2 (continued)

Question 2.4 In light of scientific issues discussed in Questions 2.1-2.3, OPP requests input from 

the SAP on factors to consider when integrating these studies in the atrazine WOE analysis 

currently under development.

3:00 P.M. Charge to Panel – Question 3 

Case Study C: Human Incident Data-- Retrospective Case Study Using Diazinon

EPA is undertaking an effort to more systematically and transparently review and use human 

incident data in risk assessment/characterization or in problem formulation than has been done 

previously. As part of this effort, a case study using human incident data on diazinon is 

included. 

Question 3.1 Case study C describes various analyses and evaluations that can be conducted 

when evaluating human incident data. Please comment on ability to use incident data for the 

following types of analyses: trend of incidents over time, frequency of reported symptoms, 

common product clusters, frequency of repeated exposure scenarios, and assessment of children 

vs. adult symptom profiles), in the diazinon case study and suggest alternative and/or additional 

analyses, if appropriate. 

Question 3.2 OPP plans to conduct analyses of human incident data like that described in Case 

study C for other pesticides undergoing registration review. In light of scientific issues 
discussed in Questions 3.1, OPP requests input from the Panel on factors to consider when 

evaluating the reliability of human incident data and determining the relative weight that should 

be placed on such data in risk assessment/characterization or in problem formulation.

NOTE: Please be advised that agenda times are approximate; when the discussion for 

one topic is completed, discussions for the next topic will begin. For further information, 

please contact the Designated Federal Official for this meeting, Myrta R. Christian, via 

telephone: (202) 564-8498; fax: (202) 564-8382; or email: christian.myrta@epa.gov

6

4:30 P.M. Adjourn 
 OPEN MEETING 

7

AGENDA 

FIFRA SCIENTIFIC ADVISORY PANEL (SAP) 

 

February 2 – 5, 2010 

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805 

Docket Number: EPA-HQ-OPP- 2009-0851 

U.S. Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.) 

2777 S. Crystal Drive, Arlington, VA 22202 

Draft Framework and Case Studies on Atrazine, Human Incidents, and the 

Agricultural Health Study: Incorporation of Epidemiology and Human Incident 

Data into Human Health Risk Assessment 

Please note that all times are approximate (see note at end of Agenda). 

Thursday, February 4, 2010 

8:30 A.M. Opening of Meeting and Administrative Procedures – Myrta R. 

Christian, M.S, Designated Federal Official, Office of Science Coordination 

and Policy, EPA 

8:35 A.M. Introduction and Identification of Panel Members – Steven G. 

Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair 

8:50 A.M. Follow-up from Previous Day’s Discussion Opening of Meeting and 

Administrative Procedures – TBD, Health Effects Division, Office of 

Pesticide Programs, EPA 

9:15 A.M. Charge to Panel – Question 4 

Case Study B: The Agricultural Health Study Comparison of Exposure Assessment 

Approaches 

The Agricultural Health Study (AHS) is a large long-term prospective epidemiological study that 

is collecting data on the health and work practices of licensed pesticide applicators in Iowa and 

North Carolina. The AHS is focusing particularly on the exposure of applicators to 50 

chemicals, including many of the most widely used pesticides. The study also collects 

information on other possible agricultural exposures, and many lifestyle factors. Investigators 

with the AHS have published over 100 publications on a variety of topics including 

characteristics of the cohort and cancer and non-cancer health outcomes that have been observed 

in the cohort (http://aghealth.nci.nih.gov/). 
Question 4.1: The Agency believes prospective epidemiology studies with robust exposure 

assessment, like the AHS, have the greatest potential for use in risk assessment especially for 

enhancing problem formulation and risk characterization. Please comment on appropriate ways 

to use of these types of epidemiology studies in risk assessment. 

Question 4.2: The Agency uses a predictive, scenario-based approach to calculate risks 

associated with the registered use patterns of pesticides. Estimates of risk based on varying 

levels of protective equipment, application methods, and use conditions are presented. The 

results of these assessments are used to specify label conditions that are required to support the 

new registration or continued registration of pesticides. In contrast, the goal of epidemiologic 

exposure assessment within the AHS is to develop a relative exposure ranking of individuals 

who are actual pesticide users within a cohort. It is not feasible to directly measure actual 

exposure in observational analyses such as the AHS. The AHS exposure information is 

ascertained from questionnaires completed by individual cohort members. Because the AHS 

and the Agency have different purposes for evaluating pesticide applicator exposure, there are 

inherent differences in the occupational handler exposure methodologies between the AHS and 

Agency. How to reconcile these differences in order to make optimal use of the AHS is 

developing regulatory policy is under investigation by a collaborative effort between EPA’s OPP 

and investigators involved with the AHS. Case study B details a three step analysis plan for 

accomplishing this goal. Please comment on the proposed plan for comparing the exposure 

assessment approaches between the Agency and the AHS. Please include in your comments the 

scientific value of this comparison along with additional and/or alternative analyses which could 

be conducted. 

8

10:30 A.M. Break 

10:45 A.M. Charge to Panel – Question 4 (continued) 

Question 4.3: The Agency has a long-term goal to understand the extent to which findings from 

the AHS are generalizable to other populations, such as pesticide applicators in states other than 

North Carolina and Iowa or those who may be exposed to pesticides through other pathways and 

under different use conditions. Please provide suggestions for analyses which could be 

conducted to make best use of the results of AHS in a broader regulatory context.

12:00 P.M. Lunch 

1:00 P.M. Charge to Panel – Discussion continued (as needed) 

2:30 P.M. Break 

2:45 P.M. Charge to Panel – Discussion continued (as needed) 

4:30 P.M. Adjourn 

NOTE: Please be advised that agenda times are approximate; when the discussion for 

one topic is completed, discussions for the next topic will begin. For further information, 

please contact the Designated Federal Official for this meeting, Myrta R. Christian, via 

telephone: (202) 564-8498; fax: (202) 564-8382; or email: christian.myrta@epa.gov
 OPEN MEETING 

9

AGENDA 

FIFRA SCIENTIFIC ADVISORY PANEL (SAP) 

 

February 2 – 5, 2010 

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805 

Docket Number: EPA-HQ-OPP- 2009-0851 

U.S. Environmental Protection Agency 

Conference Center - Lobby Level 

One Potomac Yard (South Bldg.) 

2777 S. Crystal Drive, Arlington, VA 22202 

Draft Framework and Case Studies on Atrazine, Human Incidents, and the 

Agricultural Health Study: Incorporation of Epidemiology and Human Incident 

Data into Human Health Risk Assessment 

Please note that all times are approximate (see note at end of Agenda). 

Friday, February 5, 2010 

8:30 A.M. Opening of Meeting and Administrative Procedures – Myrta R. 

Christian, M.S, Designated Federal Official, Office of Science Coordination 

and Policy, EPA 

8:35 A.M. Introduction and Identification of Panel Members – Steven G. 

Heeringa, Ph.D., FIFRA Scientific Advisory Panel Chair 

8:50 A.M. Follow-up from Previous Day’s Discussion Opening of Meeting and 

Administrative Procedures – TBD, Health Effects Division, Office of 

Pesticide Programs, EPA 

9:15 A.M. Charge to Panel – Discussion continued (as needed) 

11:30 A.M. Adjourn 

NOTE: Please be advised that agenda times are approximate; when the discussion for 

one topic is completed, discussions for the next topic will begin. For further information, 

please contact the Designated Federal Official for this meeting, Myrta R. Christian, via 

telephone: (202) 564-8498; fax: (202) 564-8382; or email: christian.myrta@epa.gov